Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects

  • Bioorg Med Chem Lett. 2002 Aug 5;12(15):1967-71. doi: 10.1016/s0960-894x(02)00303-7.
Hassan M Elokdah  1 ,  Gregory S Friedrichs ,  Sie Yearl Chai ,  Boyd L Harrison ,  John Primeau ,  Michael Chlenov ,  David L Crandall
Affiliations
  • 1. Medicinal Chemistry, Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. [email protected]
PMID: 12113820 DOI: 10.1016/s0960-894x(02)00303-7
Abstract

Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45nM. The in vivo effects of these compounds in attenuating the pressor response to angiotensin-II challenge in anesthetized rats were also investigated. An unsaturated diol metabolite exhibited in vivo efficacy at intravenous doses of 1 and 3mg/kg, while the Other metabolites, both carboxylic acids, had no significant effect at the same doses.

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